Open AccessNebivolol, a β1-adrenergic blocker, protects from peritoneal membrane damage induced during peritoneal dialysis
Author(s) -
Georgios Liappas,
Guadalupe T. González-Mateo,
Anna Rita Aguirre,
Hugo Abensur,
Patricia Albar-Vizcaíno,
Emilio González Parra,
Pilar Sandoval,
Laura García Ramírez,
Gloria del Peso,
Juan Manuel Acedo,
María Auxiliadora Bajo,
Rafael Selgas,
José Antonio Sánchez Tomero,
Manuel LópezCabrera,
Abelardo Aguilera
Publication year - 2016
Publication title -
oncotarget
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.373
H-Index - 127
ISSN - 1949-2553
DOI - 10.18632/oncotarget.8780
Subject(s) - medicine , peritoneal dialysis , nebivolol , pharmacology , beta blocker , peritoneum , cardiology , pathology , heart failure , blood pressure
Peritoneal dialysis (PD) is a form of renal replacement treatment, which employs the peritoneal membrane (PM) to eliminate toxins that cannot be removed by the kidney. The procedure itself, however, contributes to the loss of the PM ultrafiltration capacity (UFC), leading consequently to the technique malfunction. β-blockers have been considered deleterious for PM due to their association with loss of UFC and induction of fibrosis. Herein we analyzed the effects of Nebivolol, a new generation of β1-blocker, on PM alterations induced by PD fluids (PDF).In vitro: We found that mesothelial cells (MCs) express β1-adrenergic receptor. MCs were treated with TGF-β to induce mesothelial-to-mesenchymal transition (MMT) and co-treated with Nebivolol. Nebivolol reversed the TGF-β effects, decreasing extracellular matrix synthesis, and improved the fibrinolytic capacity, decreasing plasminogen activator inhibitor-1 (PAI-1) and increasing tissue-type plasminogen activator (tPA) supernatant levels. Moreover, Nebivolol partially inhibited MMT and decreased vascular endothelial growth factor (VEGF) and IL-6 levels in supernatants.In vivo: Twenty-one C57BL/6 mice were divided into 3 groups. Control group carried a catheter without PDF infusion. Study group received intraperitoneally PDF and oral Nebivolol during 30 days. PDF group received PDF alone. Nebivolol maintained the UFC and reduced PM thickness, MMT and angiogenesis promoted by PDF. It also improved the fibrinolytic capacity in PD effluents decreasing PAI-1 and IL-8 and increased tPA levels.